Thursday, September 15, 2005

Gag Clauses in Clinical-Trial Agreements

I recently came across this interesting article in the New England Journal of Medicine. It discusses the prevelance of clauses in clinical trial agreements that give the trial sponsors the de facto right to prevent publication of negative results.

Gag clauses in clinical-trial agreements prevent investigators from examining the data independently or submitting a manuscript for publication without first obtaining the consent of the sponsor. Sponsors with a financial interest in the outcome of clinical research can suppress negative results. They can also interfere with the publication of unfavorable data on safety [...]

Progress against gag clauses, however, could be forthcoming, spurred by public concern about medication safety, distrust of the pharmaceutical industry, and advocacy within the medical community for greater openness in conducting and reporting clinical trials. In December 2004, the House of Delegates of the American Medical Association committed the organization to working with industry and other groups to eliminate gag clauses in clinical-trial agreements and to "take all appropriate action to protect the rights of physician researchers to present, publish and disseminate data from clinical trials." The Fair Access to Clinical Trials Act of 2005, as introduced in the Senate by Senators Grassley and Dodd in February, would ban contracts involving researchers or their institutions that prohibit, limit, or unreasonably delay the discussion of the results of a clinical trial at a scientific meeting or the publication of results. [...]

A basic tenet of research ethics is that the data from clinical trials should be fully analyzed and published. If the knowledge gained from trials is not shared, subjects have been exposed to risk needlessly. Moreover, participants in future studies may be harmed because earlier results were not available. These principles are reflected in federal regulations regarding the protection of human subjects, which define research as "a systematic investigation designed to develop or contribute to generalizable knowledge."

Sounds good. But academics rely very much on the dollars these sponsored trials bring in. The profit often is what keeps their personal research going. Understandably, there is serious competition for sponsor contracts.

Given their educational and public-service missions and their capability of conducting unbiased and rigorous clinical trials, academic medical centers should have a vested interest in working together to eliminate gag clauses. Academic institutions, however, compete for clinical-trial research contracts with other medical centers, as well as with private groups known as contract research organizations, or CROs. These organizations can often provide research services at lower cost and with fewer administrative burdens. [...]

An academic institution whose standards for access to data and publication rights are stricter than those of its competitors may lose trials — unless it has access to unique groups of patients or its researchers have some unique expertise. [...]

A related and contentious issue is the proper definition of the phrase "access to the data." Does the sponsor control the data, perform the statistical analysis, and provide a copy of the results to the investigators? Or is the trial database made available to the researchers, who independently confirm the findings and conduct their own analyses? [...]

How might gag clauses in clinical-trial agreements be eliminated? Unless there is a federal ban, academic medical centers and other research organizations, in collaboration with leading clinical researchers, would have to develop strict policies about access to data and publication rights and adhere to them. If they did so, sponsors would be unable to seek more favorable terms from one institution than from another. Medical journals would need to strengthen their existing guidelines — for example, by explicitly defining minimum standards for authors' access to data and their right to examine the data independently, and then refusing to publish studies that do not meet these standards. In some instances, all the data might need to be made available to — and analyzed by — a statistical group that was independent of the industry sponsor. In the absence of a broad-based effort, however, the current opportunity for change may be lost.

All excellent suggestions. Lets hope the feds take the lead here and enact such a ban. Unfortunately, arrayed opposite the medical ethicists are the pharma companies, which wield enormous influence in Washington.